Genetics of African American Type 2 Diabetes Project Summary: Type 2 diabetes (T2D) is highly prevalent in the US with higher prevalence in the minority populations (9- 13.2%) as compared to non-Hispanic whites (7.6%). Efforts from large multi-ancestry consortia using genome- wide association studies (GWAS) approaches have successfully identified a large number of genetic variants associated with T2D. However, the majority of disease heritability remains unexplained and identification and characterization of the respective causal loci is limited. This is especially true for African Americans, the focus of this application, in which have led genetic exploration of type 2 diabetes genetics. Building on our establishment of the largest GWAS in African Americans in the Meta-analysis of Type 2 Diabetes in African Americans (MEDIA) Consortium and ongoing collaborations with other consortia on T2D and related traits, this project aims to use integrative phenomics analyses of genomics, metabolomics and transcriptomics in well- characterized samples to achieve the following specific aims. Aim 1: GWAS meta-analysis of baseline and dynamic glucose homeostasis traits and identification of functional variants and target genes using genomics and metabolomics. Aim 2: Integration of genomics, metabolomics and transcriptomics to identify functional variants and target genes for T2D. Aim 3: Integration of functional annotations, cross-trait associations and gene-gene/gene environment interactions to fine map T2D related loci and discover novel loci in African American and trans-ancestry GWAS.